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ABSTRACT: Co-infections can alter the host immune responses and modify the intensity and dynamics of concurrent parasitic species. The extent of this effect depends on the properties of the system and the mechanisms of host-parasite and parasite-parasite interactions. We examined the immuno-epidemiology of a chronic co-infection to reveal the immune mediated relationships between two parasites colonising independent organs, and the within-host molecular processes influencing the dynamics of infection at the host population level. The respiratory bacterium, Bordetella bronchiseptica, and the gastrointestinal helminth, Graphidium strigosum, were studied in the European rabbit (Oryctolagus cuniculus), using long-term field data and a laboratory experiment. We found that 65% of the rabbit population was co-infected with the two parasites; prevalence and intensity of co-infection increased with rabbit age and exhibited a strong seasonal pattern with the lowest values recorded during host breeding (from April to July) and the highest in the winter months. Laboratory infections showed no significant immune-mediated effects of the helminth on bacterial intensity in the lower respiratory tract but a higher abundance was observed in the nasal cavity during the chronic phase of the infection, compared with single bacterial infections. In contrast, B. bronchiseptica enhanced helminth intensity and this was consistent throughout the 4-month trial. These patterns were associated with changes in the immune profiles between singly and co-infected individuals for both parasites. This study confirmed the general observation that co-infections alter the host immune responses but also highlighted the often ignored role of bacterial infection in helminth dynamics. Additionally, we showed that G. strigosum had contrasting effects on B. bronchiseptica colonising different parts of the respiratory tract. At the host population level our findings suggest that B. bronchiseptica facilitates G. strigosum infection, and re-infection with G. strigosum assists in maintaining bacterial infection in the upper respiratory tract and thus long-term persistence.
International journal for parasitology 05/2012; 42(7):647-55. · 3.39 Impact Factor
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ABSTRACT: Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations.
PLoS Computational Biology 01/2012; 8(1):e1002345. · 5.22 Impact Factor
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ABSTRACT: The role of host immunity has been recognized as not only playing a fundamental role in the interaction between the host and pathogen but also in influencing host infectiousness and the ability to shed pathogens. Despite the interest in this area of study, and the development of theoretical work on the immuno-epidemiology of infections, little is known about the immunological processes that influence pathogen shedding patterns.
We used the respiratory bacterium Bordetella bronchiseptica and its common natural host, the rabbit, to examine the intensity and duration of oro-nasal bacteria shedding in relation to changes in the level of serum antibodies, blood cells, cytokine expression and number of bacteria colonies in the respiratory tract. Findings show that infected rabbits shed B. bronchiseptica by contact up to 4.5 months post infection. Shedding was positively affected by number of bacteria in the nasal cavity (CFU/g) but negatively influenced by serum IgG, which also contributed to the initial reduction of bacteria in the nasal cavity. Three main patterns of shedding were identified: i- bacteria were shed intermittently (46% of individuals), ii- bacteria shedding fell with the progression of the infection (31%) and iii- individuals never shed bacteria despite being infected (23%). Differences in the initial number of bacteria shed between the first two groups were associated with differences in the level of serum antibodies and white blood cells. These results suggest that the immunological conditions at the early stage of the infection may play a role in modulating the long term dynamics of B. bronchiseptica shedding.
We propose that IgG influences the threshold of bacteria in the oro-nasal cavity which then affects the intensity and duration of individual shedding. In addition, we suggest that a threshold level of infection is required for shedding, below this value individuals never shed bacteria despite being infected. The mechanisms regulating these interactions are still obscure and more studies are needed to understand the persistence of bacteria in the upper respiratory tract and the processes controlling the intensity and duration of shedding.
BMC Microbiology 01/2010; 10:226. · 3.04 Impact Factor
